Study On The Triptolide Ophthalmic Nanoemulsion Gel

Triptolide is a diterpene epoxy lactone extracted from traditional Chinese medicine Tripterygium wilfordii with anti-inflammatory,anti-cancer and immune regulation effects,generally used for the treatment of rheumatoid arthritis,skin diseases,Immunosuppression and diseases such as malignant tumors.Triptolide has poor water solubility and its clinical application has been limited.In order to overcome the shortcomings of triptolide,this paper uses the solubilization characteristics of nanoemulsion on hydrophobic drugs to improve the solubility of triptolide.The temperature-sensitive in situ gel technique is used to prolong the action time of the drug in the eye.The triptolide has a sustained release effect;the topical triptolide nanoemulsion gel preparation is prepared,and the molecular mechanism of its anti-inflammatory effect is preliminarily studied.Firstly,using poloxamer 407?P407?and poloxamer 188?P188?as the temperature-sensitive gel matrix,the concentration of the two substrates is the factor affecting the phase transition temperature,and the phase transition temperature is used as the response index to make the star point design.The optimum ratio of the temperature-sensitive gel matrix was P407:P188:H₂O=22.5:3.2:74.3?w/w?,and the temperature-sensitive gel was in a liquid state below 30.5°C,and it was in a gel state when it was greater than 30.5°C.Then,combined with the solubility experiment and the water titration method,the pseudo-ternary phase diagram was drawn,and Lbrafil M1944CS,Cremophor EL35 and Labrasol were selected as the oil phase,emulsifier and co-emulsifier of the nanoemulsion;the particle size was used as the evaluation index,and the center group and design were adopted.The ratio of the components of the nanoemulsion was optimized by the method of Lbrafil M1944CS:Cremophor EL35:Labrasol:H₂O=2:13.5:4.5:80,the average particle diameter was 20.2nm,and the polydispersity coefficient was 0.15.The stability experiment of the triptolide alcohol nanoemulsion gel prepared by the method showed that the particle size change was not obvious within 180 days,and the stability was good.The in vitro dissolution and release test results show that the triptolide nanoemulsion gel meets the zero-order kinetics.The antibacterial effect of triptolide nanoemulsion showed that the inhibition rates of Staphylococcus aureus,Aspergillus fumigatus,Fusarium solani and Candida albicans at 250?g/mL were 70%,71%,61%,respectively.And 63%,which has a better inhibitory effect on fungi than levofloxacin eye drops.The ocular retention time of the triptolide nanoemulsion gel in animals was determined by the experiment,and the retention was about 12 min,while the levofloxacin eye drops were hardly retained on the corneal surface of the rabbit eye.According to the Draize scoring principle and criteria,the results of single and multiple eye administration irritant tests showed that the triptolide nanoemulsion gel was not irritating to rabbit cornea.Finally,LPS was used to establish a model of keratitis;after treatment with triptolide nanoemulsion gel,HE staining of cornea showed that triptolide nanoemulsion gel can reduce the number of corneal inflammatory cells;Western Blot results show Triptolide nanoemulsion gel can inhibit the formation of inflammatory factors such as NF-?B,VEGF and IL-8,and reduce it to normal levels.The anti-inflammatory effect of triptolide on LPS-induced keratitis was dose-dependent.The method for preparing triptolide alcohol nanoemulsion gel has the advantages of simple process,good stability and small eye irritation,and has a broader antibacterial effect than the commonly used eye drops,and has a sustained release effect.Good ophthalmic preparation has good application prospects.